{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:58:16Z","timestamp":1792004296719,"version":"4.4.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To perform a systematic review and meta\u2010analysis of the available literature on low fetal fraction (LFF) in cell\u2010free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61\u20139.95], <jats:italic>I<\/jats:italic>\n<jats:sup>2<\/jats:sup> of heterogeneity\u00a0=\u00a00%, <jats:italic>n<\/jats:italic>\u00a0=\u00a022 studies), trisomy 18 (OR 4.46 [3.07\u20136.47], <jats:italic>I<\/jats:italic>\n<jats:sup>2<\/jats:sup>\u00a0=\u00a00%, <jats:italic>n<\/jats:italic>\u00a0=\u00a022 studies), monosomy X (OR 5.88 [2.34\u201314.78], <jats:italic>I<\/jats:italic>\n<jats:sup>2<\/jats:sup>\u00a0=\u00a018%, <jats:italic>n<\/jats:italic>\u00a0=\u00a010 studies), and triploidy (OR 36.39 [9.83\u2013134.68], <jats:italic>I<\/jats:italic>\n<jats:sup>2<\/jats:sup>\u00a0=\u00a061%, <jats:italic>n<\/jats:italic>\u00a0=\u00a06 studies), but not trisomy 21 (OR 1.25 [0.76\u20132.03], <jats:italic>I<\/jats:italic>\n<jats:sup>2<\/jats:sup>\u00a0=\u00a036%, <jats:italic>n<\/jats:italic>\u00a0=\u00a023 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78\u20139.00], <jats:italic>I<\/jats:italic>\n<jats:sup>2<\/jats:sup>\u00a0=\u00a02%, <jats:italic>n<\/jats:italic>\u00a0=\u00a011 studies). Meta\u2010analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6366","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T03:31:00Z","timestamp":1683257460000},"page":"838-853","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Association between low fetal fraction in cell\u2010free DNA screening and fetal chromosomal aberrations: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-7880","authenticated-orcid":false,"given":"Ellis C.","family":"Becking","sequence":"first","affiliation":[{"name":"Department of Obstetrics Wilhelmina Children's Hospital University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewoud","family":"Schuit","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Cochrane Netherlands University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie M. 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